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Details

Stereochemistry RACEMIC
Molecular Formula C18H23NO.ClH
Molecular Weight 305.842
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORPHENADRINE HYDROCHLORIDE

SMILES

Cl.CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2C

InChI

InChIKey=UQZKYYIKWZOKKD-UHFFFAOYSA-N
InChI=1S/C18H23NO.ClH/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;/h4-12,18H,13-14H2,1-3H3;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C18H23NO
Molecular Weight 269.3813
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular, the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
97.7 µM [IC50]
6.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DISIPAL

Approved Use

Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Launch Date

1957
Primary
DISIPAL

Approved Use

Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Launch Date

1957
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
41.89 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
49.19 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1739.15 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1772.44 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.02 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
22.29 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
7%
ORPHENADRINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
500 mg 1 times / day steady, oral
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: steady
Dose: 500 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
2 g single, intramuscular
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, intravenous
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, oral
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
AEs
PubMed

PubMed

TitleDatePubMed
Prochlorperazine in childhood: side-effects.
1977
Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes.
2001 Jun
Acute intoxication with orphenadrine and clozapine.
2001 Nov 15
Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity.
2002
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.
2003 Dec 15
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Upregulation of cytochromes P450 2B in rat liver by orphenadrine.
2003 Jun
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
Analgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers.
2004
Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer.
2004 Jan 12
Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer.
2004 Jan 12
Objective high-frequency tinnitus of middle-ear myoclonus.
2004 Mar
NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats.
2004 Nov
Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.
2004 Oct
Alternatives to levodopa in the initial treatment of early Parkinson's disease.
2005
[Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.].
2005 Apr
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.
2005 Feb 27
Dimemorfan N-demethylation by mouse liver microsomal cytochrome P450 enzymes.
2005 Jul 1
Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs.
2006 Dec
Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine.
2006 May
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer.
2006 May 24
OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice.
2006 Nov
Effects of enzyme inducers and inhibitors on the pharmacokinetics of metformin in rats: involvement of CYP2C11, 2D1 and 3A1/2 for the metabolism of metformin.
2006 Oct
Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery.
2006 Sep
Acute adverse cutaneous reaction after the concomitant use of venlafaxine and orphenadrine citrate plus paracetamol in a depressed patient.
2006 Sep
Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction.
2006 Sep
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.
2007 Apr 20
Evaluation of enantioselective binding of basic drugs to plasma by ACE.
2007 Aug
Effect of warnings in a medical journal on the use of orphenadrine.
2008 Aug
Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration.
2008 Dec
Genetic and chemical modifiers of a CUG toxicity model in Drosophila.
2008 Feb 13
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU.
2008 Jan
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells.
2008 May
Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003.
2009 Apr
Concordant up-regulation of cytochrome P450 Cyp3a11, testosterone oxidation and androgen receptor expression in mouse brain after xenobiotic treatment.
2009 Apr
Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers.
2009 Aug
The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study.
2009 Feb
The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.
2009 Jul 6
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders.
2009 Jun 3
Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients.
2009 Oct 15
Orphenadrinium picrate picric acid.
2010 Feb 24
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Patents

Sample Use Guides

Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours. Quinine-resistant leg cramps: 100 mg orally at bedtime.
Route of Administration: Other
In Vitro Use Guide
An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:27:53 GMT 2025
Edited
by admin
on Mon Mar 31 18:27:53 GMT 2025
Record UNII
UBY910DUXH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ORPHENADRINE HYDROCHLORIDE
EP   MART.   ORANGE BOOK   VANDF   WHO-DD  
Common Name English
DISIPAL
Preferred Name English
ORPHENADRINE HYDROCHLORIDE [EP IMPURITY]
Common Name English
Orphenadrine hydrochloride [WHO-DD]
Common Name English
ORPHENADRINE (CHLORIDE)
Common Name English
ORPHENADRINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
ORPHENADRINE HYDROCHLORIDE [MART.]
Common Name English
MEPHENAMIN
Brand Name English
NSC-82357
Code English
ORPHENADRINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
ORPHENADRINE HYDROCHLORIDE [VANDF]
Common Name English
ORPHENADRINE HCL
Common Name English
Classification Tree Code System Code
WHO-VATC QN04AB02
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
WHO-ATC N04AB02
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
NCI_THESAURUS C29704
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C78075
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
RXCUI
202723
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY RxNorm
EPA CompTox
DTXSID5025815
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
NSC
82357
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
FDA UNII
UBY910DUXH
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
DRUG BANK
DBSALT001021
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
PUBCHEM
9568
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
CHEBI
60902
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
CAS
341-69-5
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
SMS_ID
100000085503
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
EVMPD
SUB03547MIG
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
ECHA (EC/EINECS)
206-435-4
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
ChEMBL
CHEMBL900
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
WIKIPEDIA
Orphenadrine hydrochloride
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY